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Titanium alloys have emerged as the most successful metallic material to ever be applied in the field of biomedical engineering. This comprehensive review covers the history of titanium in medicine, the properties of titanium and its alloys, the production technologies used to produce biomedical implants, and the most common uses for titanium and its alloys, ranging from orthopedic implants to dental prosthetics and cardiovascular devices. At the core of this success lies the combination of machinability, mechanical strength, biocompatibility, and corrosion resistance. This unique combination of useful traits has positioned titanium alloys as an indispensable material for biomedical engineering applications, enabling safer, more durable, and more efficient treatments for patients affected by various kinds of pathologies. This review takes an in-depth journey into the inherent properties that define titanium alloys and which of them are advantageous for biomedical use. It explores their production techniques and the fabrication methodologies that are utilized to machine them into their final shape. The biomedical applications of titanium alloys are then categorized and described in detail, focusing on which specific advantages titanium alloys are present when compared to other materials. This review not only captures the current state of the art, but also explores the future possibilities and limitations of titanium alloys applied in the biomedical field.

Objective： This paper aimed to review the current literature on the surface modification ofintraocular lenses （IOLs）. Data Sources： All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection： The articles on the surface modification of 1OLs were included, but those on design modification and surface coating were excluded. Results： Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly （ethylene glycol）, polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO2, heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of ｜OLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion： The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

A simple surface modification method, comprising of a thin coating with gold nanoparticles (AuNPs) and fibronectin (FN), was developed to improve the biocompatibility required for cardiovascular devices. The nanocomposites from FN and AuNPs (FN-Au) were characterized by the atomic force microscopy (AFM), UV-Vis spectrophotometry (UV-Vis), and Fourier transform infrared spectroscopy (FTIR). The biocompatibility of the nanocomposites was evaluated by the response of monocytes and platelets to the material surface in vitro. FN-Au coated surfaces demonstrated low monocyte activation and platelet activation. The behavior of human umbilical cord-derived mesenchymal stem cells (MSCs) on FN-Au was further investigated. MSCs on FN-Au nanocomposites particularly that containing 43.5 ppm of AuNPs (FN-Au 43.5 ppm) showed cell proliferation, low ROS generation, as well as increases in the protein expression levels of matrix metalloproteinase-9 (MMP-9) and endothelial nitric oxide synthase (eNOS), which may account for the enhanced MSC migration on the nanocomposites. These results suggest that the FN-Au nanocomposite thin film coating may serve as a potential and simple solution for the surface modification of blood-contacting devices such as vascular grafts.

Natural extracellular matrix provides a number of distinct advantages for engineering replacement orthopedic tissue due to its intrinsic functional properties. The goal of this study was to optimize a biologically derived scaffold for tendon tissue engineering using equine flexor digitorum superficialis tendons. We investigated changes in scaffold composition and ultrastructure in response to several mechanical, detergent and enzymatic decellularization protocols using microscopic techniques and a panel of biochemical assays to evaluate total protein, collagen, glycosaminoglycan, and deoxyribonucleic acid content. Biocompatibility was also assessed with static mesenchymal stem cell (MSC) culture. Implementation of a combination of freeze/thaw cycles, incubation in 2% sodium dodecyl sulfate (SDS), trypsinization, treatment with DNase-I, and ethanol sterilization produced a non-cytotoxic biomaterial free of appreciable residual cellular debris with no significant modification of biomechanical properties. These decellularized tendon scaffolds (DTS) are suitable for complex tissue engineering applications, as they provide a clean slate for cell culture while maintaining native three-dimensional architecture.

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant Ka was 1,639 M-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated beta -CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

Polyimides (PIs) represent a benchmark for high-performance polymers on the basis of a remarkable collection of valuable traits and accessible production pathways and therefore have incited serious attention from the ever-demanding medical field. Their characteristics make them suitable for service in hostile environments and purification or sterilization by robust methods, as requested by most biomedical applications. Even if PIs are generally regarded as “biocompatible”, proper analysis and understanding of their biocompatibility and safe use in biological systems deeply needed. This mini-review is designed to encompass some of the most robust available research on the biocompatibility of various commercial or noncommercial PIs and to comprehend their potential in the biomedical area. Therefore, it considers (i) the newest concepts in the field, (ii) the chemical, (iii) physical, or (iv) manufacturing elements of PIs that could affect the subsequent biocompatibility, and, last but not least, (v) in vitro and in vivo biocompatibility assessment and (vi) reachable clinical trials involving defined polyimide structures. The main conclusion is that various PIs have the capacity to accommodate in vivo conditions in which they are able to function for a long time and can be judiciously certified as biocompatible.

The antitumour effects of benzothiazoles are well documented, but they suffer from poor aqueous solubility and lipophilicity. Apoferritin (AFt) has been identified as a potential drug delivery vehicle due to its uniform size, biocompatibility, nontoxicity and its ability to load both hydrophobic and hydrophilic agents. Both 5F 203 and GW 610 were successfully encapsulated within AFt via the nanoreactor route, with 71 and 191 molecules per AFt, respectively. The encapsulation efficiency and drug loading of GW 610 are far superior to those of 5F 203. Encapsulation enhanced the potency of 5F 203 and GW 610 in the majority of sensitive cell lines tested, while retaining their selectivity. To improve solubility and increase encapsulation efficiency of GW 610, a series of GW 608 amino acid esters were synthesised. All GW 608-AAs showed enhanced encapsulation compared to GW 610. Increased polarity appeared to hinder encapsulation while a net positive charge increased encapsulation, with > 380 molecules of GW 608-Lys molecules per AFt cage. AFt-GW 608-Lys was found to more potent than AFt-GW 610 in 4/6 sensitive cell lines tested, and up to >3x more potent. The lysyl-amide conjugate of 5F 203, Phortress, was also encapsulated within AFt, with 130 molecules per AFt cage. This increased number of molecules per AFt cage led AFt-Phortress being more potent than AFt-5F 203 in 3/4 sensitive cell lines tested. Steady release of benzothiazoles from within AFt occurs over 12 hr at physiologically relevant pH, and is controlled by electrostatic interactions between the benzothiazole and the Aft. The formulations, AFt-Phortress and AFt-GW 608-Lys, which combine the potent and selective antitumour activity of parent benzothiazoles with biocompatibility of AFt delivery vehicle, present a viable putative anticancer therapy worthy of further preclinical development.

PurposeTo introduce the materials, anatomical design, biocompatibility and clinical results of a novel cornea device.MethodsSingle piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall were lined with a porous ingrowth surface using expanded polytetrafluoroethylene (ePTFE). Full thickness macroapertures were introduced around the skirt perimeter for nutrition and hydration of the recipient cornea. The material properties of the optic were assessed with regards to Young’s modulus, light transmission, wetting behavior, as well as the bending stiffness of the skirt. Eyedrop penetrance and degradation profile were evaluated. The prototype devices were implanted healthy rabbit model using a minimally invasive intralamellar surgical technique through a 4 mm trephination site.ResultsThe final prototype has a transparent optic with a diameter of 4.60 mm anteriorly and a skirt diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native cornea with an average normalized device skirt bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92-96%. No optical damage to any device was seen in fouling experiments, with only 3 out of 33 device optics having mild superficial debris that could be wiped off. No significant difference was observed in topical drug penetrance in the device implanted eye compared to the naïve eye. The surgery is single-step and does not require a fresh donor cornea. Twelve month clinical and histopathological outcomes in healthy rabbit model showed no extrusion and low rate of infection.ConclusionsThis novel synthetic cornea device may offer enhanced tissue integration and reduced inflammation owing to its flexibility and biocompatibility leading to improved retention. Early feasibility human studies are underway.

Due to development of nanotechnology and gold nanoparticles (AuNPs) increasing use in different areas of medicine, especially in oncology, better understanding of their potential cytotoxicity is necessary to protect patients safety. Shape and size of AuNPs is an important modulator of their cytotoxicity. Therefore, we investigated the cytotoxicity of AuNPs rods (≈39 nm length, 18 nm width), AuNPs stars (≈ 215 nm) and AuNPs spheres (≈ 6.3 nm) against human fetal osteoblast (hFOB 1.19), osteosarcoma (143B, MG63) and pancreatic duct cell (hTERT-HPNE) lines by MTT and neutral-red uptake assay. Moreover, influence of AuNPs on level of proapoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) was measured by western blot. Cellular uptake of nanoparticles and ultrastructure changes were examined by transmission electron microscopy (TEM). In the present study we have proven that AuNPs stars are the most cytotoxic against human cells. We observed that cancer cells are more susceptible to AuNPs cytotoxic effect. Furthermore, AuNPs rods and AuNPs stars caused increased expression of Bax and decreased expression of Bcl-2 protein in osteosarcoma cells. We found that AuNPs penetrated through the cell membrane and caused ultrastructural changes. Our results clearly demonstrated that the cytotoxicity of AuNPs was shape-dependent. AuNPs stars with the highest anti-cancer potential were also the most cytotoxic type of tested NPs, whereas AuNPs spheres which appears to be the safest one had small anti-cancer potential.